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Series GSE237092 Query DataSets for GSE237092
Status Public on Sep 06, 2023
Title Impact of Age and Sex on neuroinflammation due to SARS-CoV2 infection in a murine model.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the worldwide COVID-19 pandemic. While SARS-CoV-2 can infect people of all ages and both sexes, senior populations are at greatest risk of severe disease and worse outcomes, and sexual dimorphism has been reported in COVID-19. COVID-19 causes damage to multiple organ systems, including the brain. Neurological symptoms are widely observed in patients with Covid-19, with many survivors suffering from persistent neurological impairment, potentially accelerating Alzheimer’s disease (AD). This study aims to investigate the mechanisms underlying the impact of age, and sex on neuroinflammation due to SARS-CoV-2 infection using mouse models.
Methods: Wild-type C57BL/6 mice were subjected to intranasal inoculation of SARS-CoV-2 lineage B.1.351, followed by daily body weight monitoring. At 7 dpi, viral burden and inflammatory cytokine/chemokine responses in the lung and brain were determined by quantitative RT-PCR, followed by immunohistochemical and transcriptomic analyses.
Results: Older age, male sex, showed increased lung viral loads and severity of SARS-CoV-2 infection in mice. No viral RNA was detected in the brains of infected mice; however, IL-6 and CCL2 mRNA increased significantly, particularly in brains of old and APOE4 mice. Unbiased brain RNA-seq/transcriptomic analysis showed that SARS-CoV-2 infection caused significant changes in gene expression profiles, and pathway analysis identified innate immunity and defense response to virus and other organisms as the major molecular networks affected in the brain by SARS-CoV-2 infection.
Conclusions: Our findings demonstrate that age, and sex, modify the progression and outcome of SARS-CoV-2 infection. SARS-CoV-2 infection triggers neuroinflammatory responses despite the lack of detectable virus in the brain. Changes in molecular networks of innate immunity and defense response to microorganisms underlie the impact of SARS-CoV-2 infection in the brain. These findings in mice mimic epidemiological and clinical observations in humans with Covid-19.
 
Overall design We performed bulk mRNA-seq to examine the transcriptomic changes associated with SARS-CoV-2 infection in wild-type mice. RNA-Seq data was collected from 12 mice (6 males & 6 female) at 10 months of age at 7 days post-infection. Sequencing was performed using Illumina NovaSeq 6000 platform, generating 20 million reads per sample on a 150-bp paired-end run.
 
Contributor(s) Krishna VD, Chang A, Korthas H, Var SR, Low WC, Li L, Cheeran MC
Citation(s) 37645925
Submission date Jul 11, 2023
Last update date Sep 06, 2023
Contact name Ling Li
E-mail(s) lil@umn.edu
Organization name University of Minnesota
Department Experimental and Clinical Pharmacology
Lab Li Lab
Street address Mcguire Translational Research Facility, 4-419
City Minneapolis
State/province MN
ZIP/Postal code 55455
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM7594666 Male 1 SARS2 [X21260]
GSM7594667 Male 2 SARS2 [X21192]
GSM7594668 Male 3 SARS2 [X21193]
Relations
BioProject PRJNA993693

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Supplementary file Size Download File type/resource
GSE237092_read_counts.xlsx 3.5 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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